敌百虫暴露对小鼠及胎鼠生殖发育影响

目的研究母鼠器官形成期经口暴露较低浓度的有机磷农药-敌百虫,对母鼠生殖功能、内分泌功能及胚胎发育的影响。方法孕鼠随机分为对照组和3个实验组,在胎儿器官形成期即妊娠第6～15d经口灌胃染毒敌百虫,剂量分别为0,12.5,25和50 mg/kg。在妊娠第17d经眼球取血后处死孕鼠,研究在本实验剂量下,敌百虫对孕鼠生殖功能、内分泌功能以及胚胎发育的影响。结果（1）母鼠器官形成期经口暴露敌百虫,可导致各实验组胎鼠外观畸形发生率显著增高（P〈0.01）。（2）各剂量敌百虫暴露对孕鼠的生育力及妊娠结局无明显影响,表现在孕鼠的体重、卵巢脏器系数、胎盘脏器系数、黄体数、着床率、活胎数、死胎数、吸收胎数等与对照组比较差异无统计学意义（P〉0.05）;（3）除50mg/kg剂量敌百虫的暴露可引起母鼠血清雌二醇浓度下降外,其他各剂量组母鼠血清和卵巢的雌二醇浓度均未见明显影响。结论在本实验剂量下,器官形成期雌鼠经口暴露敌百虫对子代胚胎的生长发育有影响,表现为胎鼠的畸形发生率增加,但对母鼠的生殖功能、内分泌功能未见明显影响。     

A cluster of congenital abnormalities particularly Down's syndrome in a small Hungarian village in 1989–90

A unique cluster of congenital abnormalities, particularly Down's syndrome and twins was detected in a small Hungarian village in 1989 and 1990. Of 15 livebirths, 11 had congenital abnormalities (within them 4 have affected by Down's syndrome) and 6 were twins. Different approaches of field studies and laboratory examinations indicated the germinal mutagenic and teratogenic effect of the excessive use of trichlorfon at local fish farms. Here the main experiences of this environmental abuse are summarised and the goals of ongoing studies are outlined.     

急性敌百虫中毒导致女性体内的氧化应激和自由基损伤

目的 :探讨急性敌百虫中毒是否导致女性中毒者体内氧化应激和自由基损伤以及其机制 .方法 :采用病例对照研究 ,用分光光度分析法检测了 5 0例急性敌百虫女性中毒者(ADWP)和 5 0例健康女性志愿者 (HWV)的血浆一氧化氮(NO)、维生素C(VC)、维生素E(VE)、β 胡萝卜素 (β CAR)含量以及红细胞丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPX)、乙酰胆碱酯酶(AChE)活性 .结果 :与HWV组 (NO ,MDA ,VC,VE,β CAR ,SOD ,CAT ,GPX和AChE分别为 (36 1± 88)nmol/L ,(2 9± 5 )nmol/g,(5 6± 1 7) μmol/L ,(2 6± 8) μmol/L ,(1 .7± 0 .5 ) μmol/L ,(2 0 5 5±1 89)kat/g,(2 97± 87)kat/g ,(2 8± 8)kkat/g和 (2 97± 86 )kkat/g比较 ,ADWP组的NO(5 2 1± 1 35 )和MDA(36± 6 )显著升高 (P<0 .0 1 ) ,VC(4 1± 1 0 ) ,VE(1 8± 5 ) ,β CAR(1 .4± 0 .4 ) ,SOD(1 799± 1 6 0 ) ,CAT(2 39± 72 ) ,GPX(2 4± 5 )和AChE(2 37± 6 0 )显著降低 (P <0 .0 1 ) ;偏相关分析提示 ,ADWP的AChE值随着NO和MDA值的升高及VC,VE,β CAR ,SOD ,CAT和GPX值的降低而降低 (r =- 0 .5 4 9,- 0 .5 84 ,0 .5 72 ,0 .4 76 ,0 .5 6 2 ,0 .6 4 1 ,0 .5 6 7和 0 .6 32 ,P <0 .0 1 ) ;对反映ADWP氧     

敌百虫暴露对孕鼠血清对氧磷酶活性及胚胎发育的影响

目的 探讨敌百虫长期低剂量暴露对孕早期血清对氧磷酶(PON)活性和胚胎发育的影响.方法 选用雌性ICR小鼠120只,随机分为空白对照组和不同剂量敌百虫染毒组,每组30只,每天分别给予0、2、10、50 mg/kg敌百虫进行染毒,连续染毒27 d后进行交配,并对孕鼠继续染毒,于孕第3天断髓处死.测定血清PON和乙酰胆碱酯酶(AchE)活性,同时观察孕鼠胚胎的发育情况.结果 血清PON活性随敌百虫染毒剂量的增加有明显下降趋势,在2、10、50 mg/kg染毒组分别为(14.15±1.22)、(12.78±1.80)、(10.45±1.95) IU/mL,其中50 mg/kg染毒组明显低于对照组的(13.37±2.31) IU/mL(P<0.01);10 mg/kg和50 mg/kg染毒组的AchE活性为(44.54±6.92) IU/mL和 (41.54±4.49) IU/mL,明显低于对照组的(51.81±6.20) IU/mL(P<0.01).各染毒组胚胎着床率和异常胚胎百分率与对照组比较差异均无统计学意义(P>0.05),但50 mg/kg染毒组异常胚胎百分率较对照组有增高趋势.结论 敌百虫长期低剂量暴露对孕鼠血清PON和AchE活性具有一定的抑制作用,对胚胎发育未见明显影响.     

Acute toxicity to freshwater organisms of antiparasitic drugs for veterinary use

The acute toxicity of five antiparasitic drugs used in the veterinary field-amprolium hydrochloride (APH), bithionol (BT), levamisole hydrochloride (LVH), pyrimethamine (PYM) and trichlorfon (TRC)-to the aquatic organisms Oryzias latipes, Daphnia magna, and Brachionus calyciflorus was examined. The toxicity test with O. latipes was conducted in accordance with the OECD Guidelines for the Testing of Chemicals (1993) to determine the 24-, 48-, 72-, and 96-h LC(50) values. In addition, 24- and 48-h EC(50) values for D. magna and a 24-h EC(50) for B. calyciflorus were determined with the DAPHTOXKIT F(trade mark) magna (Creasel, Belgium) and the ROTOXKIT F(trade mark) (Creasel, Belgium), respectively. High-performance liquid chromatographic analysis revealed that APH, LVH, and PYM were stable in water, but BT was unstable, decreasing by 84% on average at 24 h. TRC rapidly decomposed, with only 0.7% of the initial concentration remaining after 96 h, forming dichlorvos. The toxicity of TRC to O. latipes was determined in two ways: exposure to the same medicated water for 96 h (static test) and exposure to medicated water replaced every 24 h (semistatic test). AMP, LVM, and PYM were tested in the static condition, and BT was tested in the semistatic condition. BT was most toxic to O. latipes, with a 96-h LC(50) of 0.24 mg L(-1), followed by PYM, with a 96-h LC(50) of 5.6 mg L(-1). The 24-, 48-, 72-, and 96-h LC(50) values of TRC in the static test were 92.0, 45.2, 29.5, and 17.6 mg L(-1), respectively, which tended to be lower than those in the semistatic test, especially late in the observation period. D. magna was the most susceptible to TRC, with a 48-h EC(50) as low as 0.00026 mg L(-1). The 48-h EC(50) values of BT, PYM, and LVH for D. magna were 0.3, 5.2, and 64.0 mg L(-1), respectively. B. calyciflorus was the most susceptible to BT, with an EC(50) of 0.063 mg L(-1), followed by PYM, with an EC(50) of 15.0 mg L(-1). Among the test compounds, APH was the least toxic to all the freshwater organisms tested, with a 96-h LC(50) of >600 mg L(-1) for O. latipes, a 48-h EC(50) of 227 mg L(-1) for D. magna, and an EC(50) of 403 mg L(-1) for B. calyciflorus.     

粉防己碱对敌百虫中毒小鼠的保护作用

目的：验证粉防己碱对有机磷酸酯中毒动物的保护作用。方法：采用急性毒性试验,以判断粉防己碱对LD100剂量敌百虫中毒小鼠的保护作用。应用和未用粉防己碱处理的中毒小鼠死亡率间的差异显著性,以卡方测验进行检验。结果：粉防己碱（20～40 mg/kg,i.p.）对中毒小鼠有确切的保护效果,因为粉防己碱处理的动物死亡率明显低于用生理盐水处理的对照组死亡率（P＜0.05）;粉防己碱处理组的死亡率接近阿托品（10 mg/kg,i.p.）处理组的死亡率,二者之间无显著差异（P＞0.05）。结论：粉防己碱具有近似阿托品的对抗有机磷酸酯中毒功效,并提示它可被用作阿托品治疗此类毒物中毒时的协同剂。粉防己碱的作用机理目前尚不清楚,有待进一步探讨。     

Changes in Carbohydrate Metabolism in Various Organs of the Snail,Lymnaea acuminata following Exposure to Trichlorfon

Abstract: Several aspects of carbohydrate metabolism following 24 hr and 48 hr treatment with 10 and 20 mg/l of trichlorfon, were studied in hepatopancreas, mantle, intestine and foot of the snail, Lymnaea acuminata. Following treatment with the pesticide, the rate of oxygen consumption and concentration of glycogen were reduced, while the levels of lactic acid and reducing sugars were enhanced. Withdrawal of pesticide for 7 days following trichlorfon treatment (10 mg/l for 48 hrs) could not reverse these changes.     

Effect of histidine modification on the aging of organophosphate-inhibited acetylcholinesterase

Organophosphate-inhibited bovine erythrocyte acetylcholinesterase undergoes aging, a process whereby the phosphoenzyme is transformed to a form which is no longer reactivated by oximes. Aging was estimated indirectly by reactivation of trichlorfon-inhibited acetylcholinesterase by pyridine-2-aldoxime methiodide or directly by loss of tritium from [1,3-³H]diisopropylfluorophosphate inhibited enzyme. The aging of diisopropylfluorophosphate(DFP)-inhibited acetylcholinesterase was due primarily to dealkylation, rather than to the alternative β-elimination mechanism which was also examined. Aging of trichlorfon-inhibited acetylcholinesterase was not decreased by modification of sulfhydryl, carboxyl or amino groups outside the active site of the enzyme. Modification of histidine by 2 mM diethylpyrocarbonate irreversibly inhibited acetylcholinesterase activity. Dealkylation of [1,3-³H]DFP-inhibited acetylcholinesterase was slowed 2-to 3-fold by reaction of active site histidine with 2 mM diethylpyrocarbonate, and it was abolished at higher concentrations. It was concluded that an active site histidine catalyzes both aging and acetylcholine hydrolysis in erythrocyte acetylcholinesterase.     

敌百虫联合高脂饲料喂养大鼠动脉粥样硬化模型的建立

目的 探索建立类似人类长期接触低剂量、低毒性有机磷酸酯农药诱导动脉粥样硬化(As)大鼠模型的方法. 方法 健康SD大鼠,雌雄各半,随机分为普食喂养的对照组及敌百虫腹腔注射的高脂饲料喂养的模型组. 结果 第4、8周后模型组大鼠血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇LDLC及As指数(AI)均显著高于对照组(P＜0.05);HDLC/TC比值均显著低于对照组(P＜0.01);主动脉弓及肝脏形态学观察发现,模型组出现明显的As病变. 结论 本实验初步建立了As大鼠模型,可作为研究人类长期接触低剂量、低毒性有机磷农药引起的大血管病变及其药物治疗的动物模型.     

母鼠有机磷农药暴露对着床前期小鼠胚胎的细胞遗传学及生长发育的影响

[目的]研究妊娠初期有机磷农药暴露对母体生殖功能，对子代细胞遗传学及生长发育的影响。[方法]以有机磷农药敌百虫为受试物，以着床期胚胎为研究对象，以反映染色体异常的微核形成和反映胚胎生长发育状况的构成细胞数为指标。孕鼠腹腔注射100或200mg/kg剂量的敌百虫溶液，3d后，在体视显微镜下从其子宫中取出胚胎，进行其形态学分析，微核试验及胚胎构成细胞数的分析。[结果]敌百虫暴露组的胚胎微核发生率明显高于对照组，分别为200mg／kg暴露组为16．9％，100mg／kg暴露组16．1％，对照组为5．3％，并有明显的剂量-反应关系。此外，母鼠暴露于敌百虫，可造成子代生长发育迟缓，表现为胚胎构成细胞数明显下降(200mg/kg组44．1，对照组54．7)。[结论]妊娠初期有机磷农药暴露对着床前期胚胎的细胞遗传学及生长发育有明显影响。着床前期小鼠胚胎的微核试验是评价母体早期暴露有机磷农药导致子代细胞遗传学改变的简便、灵敏的指标，本结果为进一步对着床后胚胎的研究，奠定了基础。